Thyroid Function Test Results - 2: APFCB Masterclass in Interpretative Commenting

APFCB Masterclass in Interpretative Commenting
Thyroid function test results -2
Sam Vasikaran
PathWest-Laboratory Medicine WA
Perth, Western Australia
ASIA-PACIFIC FEDERATION FOR CLINICAL

BIOCHEMISTRY AND LABORATORY MEDICINE
Today’s Agenda
1. Interpretative commenting in Clinical Chemistry

 Intro / recap
2. Series of more complex TFT results

 Interpretative comments
 Note these are not case studies or discussions

Recap summary
 Most clinicians welcome appropriately applied interpretative

comments on Clinical Chemistry reports
 TFT report comments may improve patient outcomes
 Pathologists and Clinical Scientists have a duty to add value to reports

where appropriate, including through interpretative comments
RCPath (UK) guidelines for provision of
interpretative comments on biochemical reports
Comments might be appropriate when:
 a management / treatment decision is indicated by the results

 a result is unexpected
 a specific question has been posed but it is not obvious whether
the results provide the answer
 a clinician has requested a test with which they are unlikely to be
familiar
 Interpretation should be provided by an appropriately
qualified person
 Comments more appropriate for GPs and junior doctors

 but not always so - Ascertain user requirements
 Over-interpretation may be misleading
 RCPA (UK) Chemical Pathology Guidelines

Possible components of
an interpretative comment
 The absence or presence of an abnormality and

its degree or severity
 Possible implications of abnormality

 diagnosis, prognosis, change in status etc
 Suggested action/follow-up
Communication with clinicians
 To:
 Get feedback about the comments
 Agree on test protocols & diagnostic criteria
 Unusual and interesting results could be triggers for direct (verbal)

communication and discussion
Biotin interference comment
High dose Biotin (>5mg/d) may falsely decrease/increase

reported serum x/y concentrations (Z Diagnostics assay)
Contact the laboratory for further information
Provide phone number
Be aware of assay updates!

TFT results
Patient: 39-year-old female
 Patient Location: General practice
 Clinical Notes : Amenorrhoea
 TFT s
 TSH 0.03 mU/L (0.50–4.0)

 Free T4 21 pmol/L (10–20)
 TFT s
 TSH 0.03 mU/L (0.50–4.0)

 Free T4 21 pmol/L (10–20)
 Free T3 5.5 pmol/L (3.0-5.5)
 TFT s
 TSH 0.03 mU/L (0.50–4.0)

 Free T4 21 pmol/L (10–20)
 Free T3 5.5 pmol/L (3.0-5.5)
 Comment: The suppressed TSH and high/normal fT4 and fT3 suggest
hyperthyroidism. TRAb may be useful.
However, low TSH may be seen in pregnancy which should be excluded.
These results are within reference intervals for first trimester. If pregnant,
repeat TFTs in 6 weeks.
 Q: Can the lab add on a test for hCG?
 TFT s
 TSH 0.03 mU/L (0.50–4.0)

 Free T4 21 pmol/L (10–20)
 Free T3 5.5 pmol/L (3.0-5.5)
TSH reference intervals in pregnancy

1st trimester 0.02 – 2.5
2nd and 3rd trimester 0.30 – 3.0
 Clinical Notes : Annual check
 TFT s
 TSH <0.01 mU/L (0.50–4.0)

 Free T4 16 pmol/L (10–20)
 Free T3 5.5 pmol/L (3.0-5.5)
 Clinical Notes : Annual check
 TFT s
 TSH <0.01 mU/L (0.50–4.0)

 Free T4 16 pmol/L (10–20)
 Free T3 5.5 pmol/L (3.0-5.5)
 Comment:
 Clinical conditions associated with a suppressed TSH include non-toxic
goitre, subclinical hyperthyroidism and glucocorticoid therapy.
Suggest repeat TFTs in six weeks time.
 Other causes of this pattern: Excessive T4 therapy for hypothyroidism,
treated 1ry hyperthyroidism. May also be seen in the elderly. Acute
psychiatric illness may raise FT4 and/or lower TSH.
Patient: 53-year-old female (Cont’d in 6/12)
 Clinical Notes : Previous suppressed TSH

 TFT s
 TSH <0.01 mU/L (0.50–4.0)

 Free T4 17 pmol/L (10–20)
 Free T3 6.1 pmol/L (3.0-5.5)
 Comment: The increased fT3 and suppressed TSH are consistent with T3
toxicosis
 Patient Location: Emergency Department
 Clinical Notes : Severe hypertension, sweating and palpitation
 TFT s
 TSH <0.01 mU/L (0.50–4.0)

 Free T4 45 pmol/L (10–20)
 Free T3 18 pmol/L (3.0-5.5)
 TFT s
 TSH <0.01 mU/L (0.50–4.0)

 Free T4 45 pmol/L (10–20)
 Free T3 18 pmol/L (3.0-5.5)
 Comment:
The severely increased fT4 and suppressed TSH are consistent with
thyrotoxicosis. Suggest measure TRAb
 These results may be phoned urgently given the clinical presentation
 If TFTs were normal, I would suggest plasma metanephrines

 TFT s
 TSH <0.01 mU/L (0.50–4.0)
 Free T4 45 pmol/L (10–20)
 Free T3 18 pmol/L (3.0-5.5)
 TRAb 39 U/L (<1.8)
 Comment:
The severely increased fT4 and suppressed TSH and the high TRAb are
consistent with Graves’ disease.
 This patient was diagnosed with “thyroid storm”
 Patient Location: General Practice
 Clinical Notes : Started carbimazole therapy recently for Graves’
 TFT s
 TSH <0.01 mU/L (0.50–4.0)
 Free T4 7 pmol/L (10–20)
 Clinical Notes : Started carbimazole therapy recently for Graves’
 TFT s
 TSH <0.01 mU/L (0.50–4.0)
 Free T4 7 pmol/L (10–20)
 Comment:
The reduced fT4 is consistent with excessive anti-thyroid treatment. The
suppressed TSH may take many months to normalise following
commencement of ant-thyroid threatment.
 Anti-thyroid therapy initially is guided by fT4 level until TSH normalises

 Patient Location: Nuclear Medicine
 Clinical Notes : Thyroid cancer. Pre I-131 therapy
 TFT s
 TSH 120 mU/L (0.50–4.0)

 Patient Location: Nuclear Medicine
 Clinical Notes : Thyroid cancer. Pre I-131 therapy
 TFT s
 TSH 120 mU/L (0.50–4.0)
 Comment:
History noted
[Post Thyrogen (thyrotropin alpha = recombinant human TSH)]

 Patient Location: Oncology Clinic
 Clinical Notes : Thyroid cancer. Post thyroidectomy, monitoring
 TG/ATG Ref Interval
 Thyroglobulin: 31 ug/L
Thyroglobulin
 Tumour marker for thyroid cancer

 Post thyroidectomy, detectable serum Tg indicates presence of
remnant or tumour thyroid tissue
 hTSH stimulated Tg testing is recommended to unmask occult
disease in such patients
 Highly sensitive serum Tg assays may render TSH stimulation
unnecessary
 Anti-TG Antibodies, if present, interfere with Tg immunoassays
 When Tg is measured by immunoassay, Anti-TG Ab should also be
measured
 TG/ATG Ref Interval
 Thyroglobulin: 31 ug/L (*see below)
 Anti-Thyroglobulin <1 kU/L (< 4)
 *In athyrotic patients on suppressive thyroxine therapy for differentiated

thyroid cancer, thyroglobulin < 0.1 ug/L would suggest minimal risk of
recurrent cancer. Results should be interpreted in the context of serial
measurement.
An alternative scenario
 Tg and TgAb Ref Interval
 Thyroglobulin: <0.1
 Anti Thyroglobulin antibody: 14 (<4 kU/L)

 Tg and TgAb Ref Interval
 Thyroglobulin: <0.1
 Anti Thyroglobulin antibody: 14 (<4 kU/L)
 Comment: The positive anti thyroglobulin antibodies may interfere with

this thyroglobulin immunometric assay and cause a false negative result
making the thyroglobulin result unreliable.
 Anti-Tg Ab trends may be used as a surrogate tumour marker
Patient: 50-year-old male
 Clinical Notes : Family history of thyroid disease
 TFT s
 TSH 4.2 mU/L (0.50–4.0)

 Free T4 11 pmol/L (10–20)
 fT3 5.6 pmol/L (3.0-5.5)
 TPO Ab (Abbott) 876 kU/L (< 6)
 Clinical Notes : Family history of thyroid disease
 TFT s
 TSH 4.2 mU/L (0.50–4.0)

 Free T4 11 pmol/L (10–20)
 fT3 5.6 pmol/L (3.0-5.5)
 TPO Ab (Abbott) 876 kU/L (< 6)
 Comment
The mildly increased TSH with normal fT4 and raised TPO antibodies
indicate subclinical hypothyroidism due to autoimmune thyroid disease.
fT3 measurement is helpful only in hyperthyroidism.
*[we are assuming patient is not on T3 replacement]

Patient: 62 year-old male

 Clinical Notes on Request Form: On amiodarone.
 TFT s
 TSH < 0.01 mU/L (0.50-4.00)

 Free T4 23 pmol/L (10-20)
 Free T3 5.0 pmol/L (3.0-5.5)

 TFT s
 TSH < 0.01 mU/L (0.50-4.00)

 Free T4 23 pmol/L (10-20)
 Free T3 5.0 pmol/L (3.0-5.5)
 Comment:
 Amiodarone inhibits T4 to T3 conversion as well as presenting the
thyroid with a large iodine load.
 The suppressed TSH and raised fT4 may suggest amiodarone-
induced hyperthyroidism but should be interpreted in the light of
clinical findings.
Patient: 62 year-old male - 2

 TFT s
 TSH < 0.01 mU/L (0.50-4.00)

 Free T4 23 pmol/L (10-20)
 Free T3 5.0 pmol/L (3.0-5.5)
 Comment 2:
 Amiodarone inhibits T4 to T3 conversion as well as presenting the
thyroid with a large iodine load.
 Suggest consider Specialist Endocrine referral.
 Clinical Notes : Diabetes
 TFT s
 TSH 1.3 mU/L (0.50–4.0)

 fT4 26 pmol/L (10–20)
 TFT s
 TSH 1.3 mU/L (0.50–4.0)

 fT4 26 pmol/L (10–20)
 Comment
Normal TSH indicates an euthyroid state. Causes of a
raised FT4 with reduced T4/T3 conversion include non-
thyroidal illness, drugs (beta-blockers, amiodarone, heparin,
radiocontrast) and treated thyroid disease.
Suggest measure fT3 if not on treatment
 TFT s
 TSH 1.3 mU/L (0.50–4.0)

 fT4 26 pmol/L (10–20)
 fT3 6.1 pmol/L (3.0-5.5)
 TFT s
 TSH 1.3 mU/L (0.50–4.0)

 fT4 26 pmol/L (10–20)
 fT3 6.1 pmol/L (3.0-5.5)
 Comment
Results confirmed by alternative method.
Heterophile antibody excluded for TSH.
Consider specialist Endocrine referral to test for TSH
secreting tumour or thyroid hormone resistance
Previous TFTs 3 years ago
 TFT s
 TSH 1.1 mU/L (0.50–4.0)

 fT4 17 pmol/L (10–20
 Comment
Normal TSH and and T4 are consistent with an euthyroid state
 TFT s
 TSH 1.3 mU/L (0.50–4.0)

 fT4 26 pmol/L (10–20)
 fT3 6.1 pmol/L (3.0-5.5)
 Comment
Results confirmed by alternative method.
Heterophile antibody excluded for TSH.
Previous normal TFTs noted making thyroid hormone
resistance less likely. Consider specialist Endocrine referral
to investigate for TSH secreting tumour.
 TFT s
 TSH 1.3 mU/L (0.50–4.0)

 fT4 26 pmol/L (10–20)
 fT3 6.1 pmol/L (3.0-5.5)
 [alpha subunit measurement may be useful]

 Patient Location: Emergency Dept.
 Clinical Notes on Request Form: General weakness
 TFT s
 TSH < 0.01 mU/L (0.50-4.00)

 Free T4 43 pmol/L (10-20)
 Free T3 22 pmol/L (3.0-5.5)
 TFT s
 TSH < 0.01 mU/L (0.50-4.00)

 Free T4 43 pmol/L (10-20)
 Free T3 22 pmol/L (3.0-5.5)
Before commenting look at other results!

Patient: 39-year-old Asian male
 Electrolytes
 Sodium 143 mmol/L (134-146)

 Potassium 2.4 mmol/L (3.4-5.0)
 Bicarbonate 18 mmol/L (22-32)
 Urea 6.0 mmol/L (3.0-8.0)
 Creatinine 62 umol/L (60-110)
 eGFR > 90 mL/min/1.73m^2
Patient: 39-year-old Asian male
 TFT s
 TSH < 0.01 mU/L (0.50-4.00)

 Free T4 43 pmol/L (10-20)
 Free T3 22 pmol/L (3.0-5.5)
 TRAb 14.7 kU/L (< 1.0)
Comment:
Thyrotoxicosis with hypokalaemia and muscle weakness may
be consistent with thyrotoxic periodic paralysis

 Clinical Notes on Request Form: Previous raised TSH.
 TFT s
 TSH 4.5 mU/L (0.50-4.00)

 Free T4 8 pmol/L (10-20)

 Clinical Notes on Request Form: Previous raised TSH.
 TFT s
 TSH 4.5 mU/L (0.50-4.00)

 Free T4 8 pmol/L (10-20)
 Comment:
The presence of a low fT4 with only a marginal increase in TSH may
suggest pituitary insufficiency, although these results may also be seen in
non-thyroidal illness.
Suggest further pituitary investigations or Specialist Endocrine referral if
abnormalities persist.
Patient: 67 year-old female

 Clinical Notes on Request Form: Pituitary failure. On T4
 TFT s
 TSH 0.02 mU/L (0.50-4.00)

 Free T4 8 pmol/L (10-20)

 Clinical Notes on Request Form: Pituitary failure. On T4
 TFT s
 TSH 0.02 mU/L (0.50-4.00)

 Free T4 8 pmol/L (10-20)
 Comment:
FT4 should be maintained in the upper reference interval in patients
on thyroxine for 2ry hypothyroidism,
Suggest review T4 dose (and adherence to therapy) based on
clinical assessment.
 Clinical Notes on Request Form: Semicoma
Chemistry
Na 107 mmol/L 137 - 143
K 2.2 mmol/L 3.2 - 4.3
CL 68 mmol/L 102 - 111
HCO3 26 mmol/L 22 - 31
Urea 3.4 mmol/L 3.0 - 8.0
Creat 96 umol/L 70 - 100
Glu 7.9 mmol/L 3.0 - 5.5
CK 888 U/L < 150
Chol 8.7 mmol/L <5.5
Trig 1.8 mmol/L <1.8
Chemistry
Na 107 mmol/L 137 - 143
K 2.2 mmol/L 3.2 - 4.3
CL 68 mmol/L 102 - 111
HCO3 26 mmol/L 22 - 31
Urea 3.4 mmol/L 3.0 - 8.0
Creat 96 umol/L 70 - 100
Glu 7.9 mmol/L 3.0 - 5.5
CK 888 U/L < 150
Chol 8.7 mmol/L <5.5
Trig 1.8 mmol/L <1.8
Comment: This pattern of abnormalities [hyponatraemia,

hypercholesterolaemia and a raised CK due to myopathy] may be
seen in severe hypothyroidism. Suggest measure TFTs

TFTs
TSH >100 mU/L (0.50-4.00)

fT4 8 pmol/L (10-20)

TFTs
TSH >100 mU/L (0.50-4.00)

fT4 8 pmol/L (10-20)
Diagnosis: Myxoedema coma

Thank you!

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APFCB Masterclass in Interpretative Commenting

Thyroid function test results -2

ASIA-PACIFIC FEDERATION FOR CLINICAL

1. Interpretative commenting in Clinical Chemistry

2. Series of more complex TFT results

 Note these are not case studies or discussions

 Most clinicians welcome appropriately applied interpretative

 TFT report comments may improve patient outcomes

 Pathologists and Clinical Scientists have a duty to add value to reports

Comments might be appropriate when:

 a management / treatment decision is indicated by the results

 Comments more appropriate for GPs and junior doctors

 Over-interpretation may be misleading

 RCPA (UK) Chemical Pathology Guidelines

 The absence or presence of an abnormality and

 Possible implications of abnormality

 Unusual and interesting results could be triggers for direct (verbal)

High dose Biotin (>5mg/d) may falsely decrease/increase

Contact the laboratory for further information

Provide phone number

Be aware of assay updates!

 Patient Location: General practice

 Clinical Notes : Amenorrhoea

 TSH 0.03 mU/L (0.50–4.0)

 Patient Location: General practice

 Clinical Notes : Amenorrhoea

 TSH 0.03 mU/L (0.50–4.0)

 Patient Location: General practice

 Clinical Notes : Amenorrhoea

 TSH 0.03 mU/L (0.50–4.0)

 Patient Location: General practice

 Clinical Notes : Amenorrhoea

 TSH 0.03 mU/L (0.50–4.0)

TSH reference intervals in pregnancy

 Clinical Notes : Annual check

 TSH <0.01 mU/L (0.50–4.0)

 Clinical Notes : Annual check

 TSH <0.01 mU/L (0.50–4.0)

 Patient Location: General practice

 Clinical Notes : Previous suppressed TSH

 TSH <0.01 mU/L (0.50–4.0)

 Patient Location: Emergency Department

 Clinical Notes : Severe hypertension, sweating and palpitation

 TSH <0.01 mU/L (0.50–4.0)

 Patient Location: Emergency Department

 Clinical Notes : Severe hypertension, sweating and palpitation

 TSH <0.01 mU/L (0.50–4.0)

 If TFTs were normal, I would suggest plasma metanephrines

 Patient Location: Emergency Department

 Clinical Notes : Severe hypertension, sweating and palpitation

 Patient Location: General Practice

 Clinical Notes : Started carbimazole therapy recently for Graves’

 Patient Location: General Practice

 Clinical Notes : Started carbimazole therapy recently for Graves’

 Anti-thyroid therapy initially is guided by fT4 level until TSH normalises

 Patient Location: Nuclear Medicine

 Clinical Notes : Thyroid cancer. Pre I-131 therapy

 TSH 120 mU/L (0.50–4.0)

 Patient Location: Nuclear Medicine

 Clinical Notes : Thyroid cancer. Pre I-131 therapy

 TSH 120 mU/L (0.50–4.0)

[Post Thyrogen (thyrotropin alpha = recombinant human TSH)]

 Patient Location: Oncology Clinic